Like many biological processes, transcription is controlled by both stimulatory and inhibitory proteins whose interplay regulates the overall activity of RNA polymerase II. The majority of regulatory proteins target specific genes through interaction with defined DNA elements in the proximity of or at a distance from the start site of transcription. In many instances, activators influence the activity of RNA polymerase II through direct or indirect interactions with the general transcription factors (Conaway and Conaway, (1993) Annu. Rev. Biochem. 62: 161-190; Zawel and Reinberg, (1995) Annu. Rev. Biochem. 64: 533-561). In cells, transcription is also negatively regulated by another family of factors. These factors repress transcription by different modes. Some are sequence-specific DNA binding proteins, which upon binding to specific promoters, render the gene silent (Hanna-Rose and Hansen, (1996) Trends Genet. 12: 229-234; Shi et al., (1991) Cell 67: 377-388). Other gene-specific repressors inhibit transcription by sequestering activators and preventing their translocation to the nucleus and/or preventing their association with promoter sequences (Benezra et al., (1990) Cell 61: 49-59; Baeuerle and Batimore (1988) Science 242: 540-545). Another growing family of repressors includes molecules that are tethered to promoters by interacting with sequence-specific DNA binding proteins and/or components of the basal transcription machinery (Ayer et al., (1995) Cell 80: 767-776; Inostroza et al., (1992) Cell 70: 477-489). One member of this last category is the Dr1/DRAP1 repressor complex.
Dr1 is a TATA-binding protein (TBP)-associated phosphoprotein and functions as an inhibitor of gene transcription (Inostroza et al., (1992) Cell 70: 477-489). Dr1 genes have been isolated from human, yeast, and Arabidopsis (Inostroza et al., (1992) Cell 70: 477-489; Kim et al., (1997) Proc. Natl. Acad. Sci. USA 94: 820-825; Kuromori et al., (1994) Nucleic Acids Research 22: 5296-5301). Effective repression by Dr1 requires a Dr1-associated polypeptide (DRAP1), a corepressor of transcription. Association of DRAP1 with Dr1 results in higher stability of the Dr1-TBP-TATA motif complex and precludes the entry of TFIIA and/or TFIIB to preinitiation complexes (Mermelstein et al., (1996) Genes & Development 10: 1033-1048). In eukaryotic systems, Dr1 and DRAP1 appear to form a heterodimer complex to repress gene transcription at the initiation complex formation (Inostroza et al., (1992) Cell 70: 477-489; White et al., (1994) Science 266: 448-450; Kim et al., (1995) J. Biol. Chem. 270: 10976-10981, (1996) J. Biol. Chem. 271: 18405-18412, (1997) Natl. Acad. sci. USA 94: 820-825, (2000) Mol. Cell. Biol 20:2455-2465; Goppelt et al., (1996) EMBO J. 15: 3105-3116; Gadbois et al., (1997) Proc Natl Acad Sci USA. 94:3145-50; Prelish (1997) Mol. Cell. Biol. 17: 2057-2065; Yeung et al., (1997) Mol. Cell. Biol. 17: 36-45; Cang et al., (1999) EMBO J. 18: 6662-6671; Xie et al., (2000) EMBO J 19: 672-682). DRAP1 genes have only been isolated from human and yeast (Mermelstein et al., (1996) Genes & Development 10: 1033-1048; Kim et al., (1997) Proc. Natl. Acad. Sci. USA 94: 820-825) and no plant DRAP1 proteins have been reported.
Accordingly, the availability of nucleic acid sequences encoding all or a portion of a Dr1 or DRAP1 transcriptional control protein would facilitate engineering, methods to alter gene expression in plants, and facilitate studies to better understand transcriptional regulation mechanisms in plants. Dr1 and DRAP1 proteins may also provide targets to facilitate design and/or identification of inhibitors of Dr1 and DRAP1 proteins that may be useful as herbicides.